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没药醇酮 1(MCA-1)对小鼠巨噬细胞炎症反应的抑制作用。

Inhibitory Effects of Myrtucommuacetalone 1 (MCA-1) from on Inflammatory Response in Mouse Macrophages.

机构信息

Dr Panjwani Center For Molecular Medicine and Drug Research, University of Karachi, Karachi 75270, Pakistan.

Faculty of Pharmacy, Northern Border University, Rafha 91911, Saudi Arabia.

出版信息

Molecules. 2019 Dec 18;25(1):13. doi: 10.3390/molecules25010013.

Abstract

(1) Introduction: Reactive oxygen species (ROS) and nitric oxide (NO) are key signaling molecules that play important roles in the progression of inflammatory disorders. The objective of this study was to explore the use of myrtucommuacetalone-1 (MCA-1), as a novel compound of natural origin and a potential anti-inflammatory agent. (2) Methodology: The anti-inflammatory potential of MCA-1, which was isolated from Linn, was determined by assaying superoxide, hydrogen peroxide, and nitric oxide production in macrophages. Furthermore, the effects of the compound were analyzed via phosphorylation and translocation of the transcription factor NF kappa B, which is a key regulator of iNOS activation. The effect of MCA-1 on the inducible nitric oxide synthase (iNOS) enzyme was also examined using in silico docking studies. The anticancer potential for MCA-1 was evaluated with an MTT cytotoxic assay. (3) Results: In stimulated macrophages, MCA-1 inhibited superoxide production by 48%, hydrogen peroxide by 53%, and nitric oxide (NO) with an IC of <1 µg/mL. MCA-1 also showed a very strong binding pattern within the active site of the inducible nitric oxide synthase enzyme. Furthermore, 25 µg/mL of MCA-1 inhibited inducible nitric oxide synthase expression and abolished transcription factor (NFκB) phosphorylation and translocation to the nucleus. Cytotoxicity analyses of MCA-1 on 3T3 mouse fibroblasts, CC1 liver cell line, J774.2, macrophages and MDBK bovine kidney epithelial cell, yielded IC values of 6.53 ± 1.2, 4.6 ± 0.7, 5 ± 0.8, and 4.6 ± 0.7, µg/mL, respectively. (4) Conclusion: Our results suggest that MCA-1, a major phloroglucinol-type compound, shows strong anti-inflammatory activity and has a potential to be a leading therapeutic agent in the future.

摘要

(1) 简介:活性氧(ROS)和一氧化氮(NO)是关键的信号分子,在炎症性疾病的进展中发挥重要作用。本研究的目的是探索使用从 Linn 中分离得到的新型天然产物化合物 myrtucommuacetalone-1(MCA-1)作为一种潜在的抗炎药物。

(2) 方法:通过检测巨噬细胞中超氧阴离子、过氧化氢和一氧化氮的产生来确定 MCA-1 的抗炎潜力。此外,还通过分析转录因子 NF-κB 的磷酸化和易位来分析化合物的作用,NF-κB 是 iNOS 激活的关键调节因子。还通过计算机对接研究来研究 MCA-1 对诱导型一氧化氮合酶(iNOS)酶的影响。使用 MTT 细胞毒性测定法评估 MCA-1 的抗癌潜力。

(3) 结果:在刺激的巨噬细胞中,MCA-1 抑制超氧阴离子的产生 48%,抑制过氧化氢的产生 53%,IC50 <1µg/mL 时可抑制一氧化氮(NO)的产生。MCA-1 还在诱导型一氧化氮合酶酶的活性部位表现出非常强的结合模式。此外,25µg/mL 的 MCA-1 抑制诱导型一氧化氮合酶的表达,并消除转录因子(NFκB)的磷酸化和向核内易位。MCA-1 对 3T3 小鼠成纤维细胞、CC1 肝细胞系、J774.2 巨噬细胞和 MDBK 牛肾上皮细胞的细胞毒性分析,IC50 值分别为 6.53±1.2、4.6±0.7、5±0.8 和 4.6±0.7µg/mL。

(4) 结论:我们的结果表明,作为主要的邻苯三酚型化合物,MCA-1 表现出很强的抗炎活性,并有潜力成为未来的主要治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/80ed/6983223/d3cf1ff90a49/molecules-25-00013-g001a.jpg

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